MALARIA: Zimbabwe: at pre-elimination stage

"Zimbabwe is doing very well as far as malaria control is concerned," she said in Harare. "In fact, in some areas of Matabeleland we have reached the pre-elimination stage which means our system is very advanced and meets WHO standards.”
However, when asked why the same World Health Organisation, which has developed a new drug to combat malaria, had side-lined Zimbabwe from receiving the drug, the official said: "I am not aware of this information."
The WHO said Zimbabwe was very disappointing because its malaria cases were increasing instead of decreasing, therefore it would not test its new vaccine until the disease was "fully" controlled.
At a closed workshop, a WHO spokesperson said: "The WHO has indeed developed a new drug to combat malaria. Unfortunately Zimbabwe will not benefit from this drug just yet because its cases have not been consistent with WHO standards. While we are happy about the progress made by Zimbabwe, its cases go up and down, and we want them to remain down."
She said other African countries, mainly in the West, were already benefitting from the new drug.
http://www.thezimbabwean.co.uk/news/zimbabwe/55248/malaria-campaign-impressive-nihr.html?utm_source=thezim&utm_medium=homepage&utm_campaign=listarticle&utm_content=textlink

MALARIA: More than a shield: The RTS,S malaria vaccine trial

6 Dec, 2011: Meera Senthilingam
Meera Senthilingam is a freelance science journalist based in London, UK.
 My ride to the clinic

The RTS,S vaccine is one of the most promising malaria vaccine for years, currently doing well in clinical trials. And the benefits of the trial go beyond the vaccine itself, as Meera Senthilingam discovered.
On a recent trip to Kenya, I decided to visit the quiet, coastal town of Kilifi. Unlike the busy, tourist laden beaches of Mombasa just 60 kilometres to the North, Kilifi is scenic, peaceful and far less polluted. But it also has one of the highest prevalences of disease in the country. Its warm, moist climate, combined with a poor population, mean that diseases such as malaria are quite common. As a result, Kilifi is a trial site for many malaria treatments and vaccines, including the RTS,S vaccine, the most developed malaria vaccine to date.
RTS,S has now reached phase III clinical trials involving over 15,000 participants across seven African countries. Of the eleven trial sites across these countries, three are in Kenya, taking place at the Kenya Medical Research Institute (KEMRI) bases in Kisumu in Western Kenya and, of course, Kilifi.
Equipped with a four-wheel drive and a few medical deliveries, Dr Patricia Njuguna, the principle investigator on the Kilifi trial, took me to see how such a large-scale trial works in the field. Our destination was the Madamani dispensary, one of the three clinics conducting the trial within Kilifi.
We passed acres of land where drought was evident by the dry soils followed, surprisingly, by a conserved area of natural forest. But as farmland and forest turned to huts, wells and people going about their daily lives, the car made numerous stops for women and their children to come aboard. Although initially confused as to whether the KEMRI vehicle doubled up as a taxi to increase funding, I soon learned this was all part of the service offered as part of the vaccine trial.
“As well as routine visits, if participants are unwell we provide them access to the facility for free healthcare,” says Njuguna. “Our vehicles come in every day bringing in mothers from various homes. This is coordinated by fieldworkers living within the community who have close contact with the mothers who call them when they need to be seen”.
Our driver was one of these fieldworkers and the women on board had called him that morning about various ailments affecting their children. They joined us for the remainder of the journey so their children could be examined examination by the local clinician.
The trial it seems is not just the testing of a vaccine, but a complete health service, and a very good one at that.
 Rapid malaria test

Developing a vaccine
In Sub-Saharan Africa, malaria is caused predominantly by infection with the parasite Plasmodium falciparum. Creating a vaccine has been a challenge to date due to the fact that the parasite, and its genome, is larger than bacteria and viruses, the complex nature of the parasite’s life-cycle and the fact that it can alter the proteins on its surface, limiting our ability to design a vaccine to find it and induce an immune response.
“Imagine Joseph and his Technicolor Dreamcoat that’s showing a different colour every time. If you’re trying to take down someone in red and the coat shows blue, you’ll miss it,” says Dr. Njuguna as we draw closer to the dispensary.
“This is the challenge for the vaccine and if it misses it you get malaria. Every time the parasite goes through a life cycle it changes the protein it’s presenting, so your vaccine needs to be very clever”.
Once bitten by an infected mosquito, the parasite enters the body in its immature form, known as a sporozoite, where it then travels to the liver in order to replicate within liver cells before moving on to invade red blood cells. This latter stage is when the main symptoms of disease, such as fever and chills, occur, and it’s also when the rapid production of new proteins takes place as the parasite frantically replicates within the blood cells.
RTS,S aims to overcome these issues of adaptation by targeting the parasite early on in its life cycle the sporozoite stage when the parasite first enters through the skin and travels to the liver This can happen within 3–5 minutes of infection.
When we arrive at the dispensary the first thing I notice is the high degree of organisation on site. As we enter the building, we walk straight into a large waiting room catering comfortably for tens of people at one time. Away from this stems two consultation rooms and a pharmacy. The clinician, Dr Pauline Akoo, is busy examining a child in one of the rooms while the women from our car journey are registered by fieldworkers noting down the symptoms of their children.
The trial targets two age groups of children, both under the age of 5 as this is the group at most risk of infection with malaria. The first cohort is made up of children aged 5 to 17 months and the second are infants aged 6 to 12 weeks all receiving three monthly injections followed by a booster vaccine 18 months later. This is, however, a randomised trial, so half of the participants act as a control group receiving a pretend vaccine. By comparing the number of children experiencing Malaria for the first time within each group, the researchers will see if the vaccine really has an effect.
As I join Dr Akoo for a few of her consultations, mothers bring in children with ear infections, upper respiratory tract infections and fevers. Any child brought in with a fever is given a rapid malaria test to, which diagnoses on site, allowing for immediate prescription of anti-malarials, if need be, while a sample is sent to a lab for confirmation. Medicines for the other ailments are also prescribed.
“Each time the child visits they get an opportunity to be seen by a clinician. Whether they’ve come for screening, vaccination, or some other problem they will always get a thorough medical examination,” says Akoo. This is a complete medical package for participants, and, more importantly, it is free of charge.
With such care provided in an otherwise poor region, it’s easy to imagine the flooding of volunteers to the dispensary but, as with many trials in developing regions, there was some initial anxiety and resistance.
“Initially they were shy because this is a research-naïve area – they don’t understand the difference between research and treatment,” says Akoo. “But with time we have explained the trial and the people realised it would not harm them and there were health benefits.”

 Madamani dispensary charter

Vaccine on the horizon?
RTS,S is the first vaccine to reach Phase III of clinical trials, with Phase II trial results demonstrating 53 per cent protection against malaria in children aged 5 to 17 months. Phase III is currently halfway through its intended timeframe, with encouraging preliminary results published recently in the New England Journal of Medicine.
The early results analysed 6000 of the trial participants across Africa and demonstrated 56 per cent protection against standard clinical malaria and 47 per cent against severe malaria (when the parasite enters the brain). However these results are, again, for a subsection of the study – the cohort aged 5 to 17 months – with results from the infant group expected by the end of 2012.
Without getting our hopes up too high, it does look like a vaccine against malaria could soon become a reality. Even the costs of scaling up and production have been accounted for, with pharmaceutical company GlaxoSmithKline promising to provide it almost at cost price with any return invested back into further improvement of the vaccine.
Although incidence of malaria has been on the decline in recent years, according to the World Health Organization, 781,000 people still died of the disease in 2009 – 90 per cent in Africa. Although a 56 per cent success rate may not sound significant enough to justify rolling the RTS,S out in a wider scale, when the burden of disease is considered globally, it’s certainly worth having. And from what I saw at the dispensary, the RTS,S trial has not only provided a possible shield against malaria, but also improved the understanding, and general well-being, of the people most affected by it.
The KEMRI-Wellcome Trust Research Programme is supported by the Wellcome Trust.
http://wellcometrust.wordpress.com/2011/12/06/more-than-a-shield-the-rtss-malaria-vaccine-trial/#more-7757

MALARIA: Vac-4-All and MRTC

Vac-4-All and MRTC : Launch multi-centre Malaria Vaccine Efficacy Trial in Mali
Vac-4-All, a new vaccine development initiative, and the Malaria Research and Training Centre (MRTC), a public research and training facility of the University of Bamako in the Republic of Mali, have completed the immunizations of Malian children with MSP3, a malaria vaccine prototype which recently produced promising results in a small scale trial in Burkina Faso 1.
Malaria is one of the most prominent public health problem affecting children and pregnant women in developing countries, with nearly 2.5 Billion individuals exposed, a few hundred Millions infected, and close to 1 Million deaths per year.
The trial capitalizes on the knowledge of host-parasite immune interactions and the clinical expertise accumulated by the two groups. The partnership forged between the groups intends to develop affordable vaccines against malaria and this trial is the first of a series of trials being planned to investigate several novel malaria vaccine candidates.
800 children aged 12 – 42 months are enrolled in the multi-centre double-blind, randomised, controlled Phase IIb efficacy trial. It is designed to provide a clear-cut demonstration of the efficacy of the target antigen, MSP3, in preventing clinical malaria episodes, and the underlying immunological mechanism. With an average incidence of 3 malaria attacks per person per year in the study areas, 2,400 malaria episodes are expected in the study population each year. The children are distributed across 8 villages, which are located in 2 regions which differ by their exposure to malaria, one with seasonal transmission and the other with perennial transmission, both at very high level.
Cases will be actively followed-up over 2 years post-vaccination by a large Medical team, headed by M.Sissoko and I.Sagara, with staff stationed in dispensaries in each hamlet. Particular attention has been given to the conditions of community-based and individual informed consent and participation2, to the design and organisation of the trial, to the definition criteria for clinical malaria, and to the identification of surrogate markers of protection.
About Vac4All: Vac-4-All is a private venture dedicated to malaria vaccine development, created in 2010 by P. Druilhe, formerly Head of the Malaria Vaccine Development Laboratory at the Institut Pasteur in Paris. Its mission is address urgent public health needs by developing vaccines that can be produced in a straightforward manner and that will be affordable to the populations in under-developed countries that need it most. The Vac-4-All approach follows a rationale that capatilizes on the analysis of immunological interactions between P.falciparum (the microbe that causes Malaria) and human beings which has led to the identification of several vaccine candidate molecules, explore potential surrogate markers of protection identified by clinical investigations in humans, and uses state-of–the–art research tools to analyse results from clinical trials to rationally guide product development.
About MRTC: the Malaria Research and Training Center, at the University of Bamako, in the Republic of Mali, is one of the widest malaria research facilities on the African continent and one with long-standing experience in conducting malaria clinical trials. Headed by Professor Ogobara Doumbo, its mission is to train and promote promising Malian and African doctors and scientists to work on state-of-the-art human malaria research projects and to conduct GCP/ICH-standard clinical trials with promising prophylactic and therapeutic novel compounds which could contribute to solving the problem of malaria in Africa. It is a partnership initiative, created by the MoE and MoH of Mali with technical and funding support from diverse partners including the US NIAID/NIH, TDR/WHO, the Rockfeller Foundation, and different universities (France, Italy, USA). MRTC works in close collaboration with Mali’s National Malaria Control Program and other national public institutions and with a large number of research groups over the world. Its past contributions in this field have gained international recognition.

Further information-----------------------------------------------------------------------------------------------------------------------------------
Prof. Ogobara Doumbo, Malaria Research and Training Center (MRTC), University of Bamako, BP 1805, Point G, Bamako, Republic of Mali. Mail : okd@icermali.org Phone : +223-222-8109 Fax: +223-222-8109

MALARIA: vaccine hope after blood entry route discovered

9 November 2011 James Gallagher: Health reporter, BBC News

 Malaria is transmitted by mosquitoes

The route all strains of the most deadly malaria parasite use to enter red blood cells has been identified by researchers at the Sanger Institute in Cambridge.
The scientists involved said the finding offered "great hope" for the development of a vaccine, which had the potential to be hugely effective.
Other experts said they were surprised and impressed.
Malaria affects 300 million people each year.
One million die, mostly children in sub-Saharan Africa.
There are many malaria parasites. Plasmodium falciparum is the most deadly and researchers at the Sanger Institute acknowledge it as a "very complex and cunning foe".
It is exceptionally good at evading and bamboozling the immune system. Within five minutes of being bitten by a malaria-carrying mosquito, the parasite is already hiding inside the liver.
It then emerges from the liver at a different stage in its life cycle and infects red blood cells, where it starts reproducing.
Difficulty
The human immune system struggles to build up resistance to malaria and researchers have struggled in the laboratory.
There is still no approved vaccine against malaria. Large scale trials of the most advanced prototype - RTS,S - showed it halved the risk of getting malaria.

 The parasite reproduces in red blood cells (infected cell on the right).

 

This study, published in Nature, looked at the moment the parasite infected a red blood cell.

They were looking for proteins on the surface of Plasmodium and red blood cells which were necessary for the parasite to identify its target and invade.
Others had been found before, but none were universally used.
The team at the Sanger Institute discovered that "basigin", a receptor on the surface on red blood cells, and "PfRh5", a protein on the parasite, were crucial.
In all strains of Plasmodium falciparum tested so far, interrupting the link protected the blood cells from attack.
One of the researchers, Dr Julian Rayner, said: "We were able to completely block invasion using multiple different methods, using antibodies targeting this interaction we could stop all invasion of red blood cells.
"It seems to be essential for invasion."
The plan is to develop a vaccine which will prime the immune system to attack PfRh5 on the parasite
Fellow researcher Dr Gavin Wright said a vaccine would have great potential as the target was so essential.
"As a starting point for developing a vaccine you couldn't hope for better," he said.
Prof Adrian Hill, director of the Jenner Institute at Oxford University, said that after 25 years studying malaria he was "surprised" and "intrigued" by the findings.
He said textbooks and academic research suggested that if you blocked one pathway into the red blood cells, the parasite would choose another.
He added: "It remains to be seen how easy it will be to translate into a vaccine, but [for blood stage vaccines] PfRh5 is now at the top of the list.
"Vaccine candidates will come. If I had to bet, I'd say you'd get some partial efficacy from it."
http://www.bbc.co.uk/news/health-15624363

MALARIA: New vaccination strategy fights malaria better

16 Jun 2011 : The Times of India
Scientists have discovered a powerful strategy to combat malaria that may be described as the most effective next-generation vaccination approach for the disease. The new approach works by eliciting an immune response that can combat the malarial parasite during multiple stages of its complex life cycle. "Halting Plasmodium infection during the clinically silent liver stage represents an attractive goal of antimalarial vaccination, but is challenging because, if not complete, some parasites can get into the blood and cause disease," noted study co-author Stefan Kappe, from the Seattle Biomedical Research Institute.
Irradiating the parasites elicits extensive and random DNA damage that arrests the parasite early in the liver and provides the immune system with an opportunity to develop an immune response that can combat the native parasite. However, very high irradiated-sporozoites doses are needed to generate full liver-stage protection and there is no protection against blood stages.

"In our study, we examined whether genetically attenuated parasites (GAP) generated by targeted gene deletions to stop replication late in liver-stage development were a better vaccine option," said co-author John Harty from the University of Iowa. Using mouse malaria models, the researchers discovered that immunization with late-liver-stage-arresting GAP provided superior and long-lasting protection against liver-stage infection when compared with irradiated parasites or early-liver-stage arresting GAP.
Importantly, late-liver-stage-arresting GAP also provided protection at the blood stage of infection and across different malaria parasite species, as well as by the route of immunization that can be used in humans. The research was published online in the journal Cell Host and Microbe , June 15.
http://timesofindia.indiatimes.com/life-style/health-fitness/health/New-vaccination-strategy-fights-malaria-better/articleshow/8877334.cms

MALARIA: vaccine could have extra benefits

LILONGWE, 20 June 2011 (IRIN)

 Photo: SAHIMS
Children who received the vaccine are monitored for malaria

The malaria vaccine that has eluded medical science for decades is now within reach, with the final phase of clinical trials underway in seven African countries, including Malawi, where the disease claims 6,500 lives a year, most of them children under the age of five.
Tisungane Mvalo, head of the research team at the Malawian trial site, which is being run in partnership with the University of North Carolina's Institute for Global Health and Infectious Diseases, said the current methods for controlling the incidence of malaria in Malawi have had limited success.
"We have had a moderate reduction in infant mortality from interventions like bed nets and insecticides but malaria remains the leading cause of infant mortality," he said. "There still needs to be an additional intervention."
The multi-country trial of the malaria vaccine RTS,S, made by GlaxoSmithKline Biologicals, is one of the largest ever carried out in sub-Saharan Africa. With funding from GlaxoSmithKline and the PATH Malaria Vaccine Initiative - an NGO that develops research for malaria - 15,000 newborns and infants are being inoculated at 11 sites across the region.
The children are then monitored over a period of 36 months to assess the effectiveness of RTS,S, which in previous studies reduced cases of severe malaria in infants by 53 percent. If the results, due to be released later this, year confirm the vaccine's efficacy in preventing malaria, it could be made available as early as 2015.
"It's a very exciting time," said PATH Director Dr Christian Loucq, speaking from his office in Washington. "We have estimated in our models that a vaccine like this could save hundreds of thousands of lives a year."

The high cost of malaria
A malaria vaccine would not only save lives, it would also alleviate the great burden of the disease on health systems in economically stretched developing countries.
Dr Karl Seydel, a paediatrician at Queen Elizabeth Central Hospital in Blantyre, Malawi, said the impact of the disease on the public health system was "overwhelming" - 5.5 million cases of malaria, equivalent to a third of the country's population, were reported in 2010.
"It drains the resources," he told IRIN. "We could use that money for other things; we could build more hospitals or hire more nurses."
We have estimated...that a vaccine like this could save hundreds of thousands of lives a year
He estimated that during the rainy season, when bites from mosquitoes infected with the malaria parasite are most common, about half of all admissions to the hospital's paediatric ward were due to malaria. The ward was designed for 150 patients but often has to accommodate twice that number.
Malawi has a good track record for immunizing children: 98 percent have received the standard vaccines recommended by the World Health Organization (WHO). The addition of a malaria vaccine, even at 50 percent effectiveness, could greatly reduce the number of children needing expensive hospital care.
Malaria prevention has been less successful than was hoped. According to the 2010 Malawi Demographic and Health Survey, about 70 percent of households have bed nets, but just half the children under five are using them.
Mvalo said the adults in a household often used the nets, even though children are most susceptible to developing severe malaria. In some parts of the country mosquitoes have also started showing resistance to insecticides.
"Each control method has its shortfalls," Mvalo said. "That is why a vaccine is a good alternative - not a replacement, but a good alternative."
Most researchers agree that a malaria vaccine will not substitute for current preventative measures, but could greatly reduce mortality from the disease and create huge financial gains for countries where malaria is endemic. Public health researchers estimate that in such countries, malaria directly absorbs one percent of GDP, excluding indirect costs like loss of work hours.
"Solving the problem of malaria would very much help in terms of economic development," said Loucq.
http://www.irinnews.org/report.aspx?reportID=93024

PATH Malaria Vaccine Initiative to collaborate with GlaxoSmithKline and Crucell in development of second-generation malaria vaccine

Project will combine two promising vaccine approaches to potentially improve immune responses
WASHINGTON, DC, June 7, 2011 — The PATH Malaria Vaccine Initiative (MVI) announced today that it has entered into a collaboration with Dutch biopharmaceutical company Crucell N.V. and GlaxoSmithKline (GSK). This collaboration is aimed at developing a second-generation vaccine against malaria—a deadly disease that kills close to 800,000 people annually, most of them young children under age five in Africa. MVI drives the development of malaria vaccines by joining its scientific, managerial, and field expertise with companies, universities, and governments to test potential malaria vaccines and invest in those with the most promise.
The new project will bring together two promising vaccine approaches in an effort to develop a malaria vaccine that may have the potential to improve on the efficacy of GSK’s first generation RTS,S vaccine candidate. In this collaborative effort, a single dose of Crucell’s weakened recombinant adenovirus Ad35.CS.01malaria vaccine approach will be administered, followed by two doses of GSK’s RTS,S malaria vaccine candidate in a Phase 1/2a clinical trial that is expected to begin later this year. This would be the first test in humans of this “heterologous prime-boost” approach against malaria.
“We are at an important moment in malaria vaccine development,” said Dr. Christian Loucq, director of MVI. “For the first time, we have a malaria vaccine in late phase development in the form of the RTS,S vaccine candidate. This new collaboration, though in the early stages, gives us the opportunity to test an approach with the potential to substantially increase efficacy and move us closer to the internationally agreed upon goal of an 80 percent effective second-generation vaccine by 2025.”
The RTS,S vaccine candidate is currently in the midst of a large-scale Phase 3 clinical efficacy trial. If all goes well in Phase 3 testing, the World Health Organization (WHO) has indicated that a policy recommendation for RTS,S is possible as early as 2015, paving the way for countries to make a decision about implementation through their national immunization programs. The RTS,S trial, which is the outcome of a decade-long collaboration between MVI and GSK, involves 11 sites in seven African countries.
Crucell and MVI first began working together in 2007 to develop adenovirus-based vaccines targeting malaria and are currently collaborating on another heterologous prime-boost approach. Crucell’s Ad35.CS.01 was recently tested in a Phase 1 clinical study in the United States.
RTS,S is a circumsporozoite protein (CSP)-based pre-erythrocytic P. falciparum malaria vaccine candidate that incorporates GSK’s AS01 adjuvant. Crucell’s Ad35.CS.01 vaccine approach uses a weakened, recombinant adenovirus (a type of virus associated with the common cold and other mild respiratory infections) to deliver a malaria antigen to the immune system.
In preclinical studies, the regimen to be evaluated under the new MVI-GSK-Crucell collaboration has shown enhanced immunogenicity when compared to either vaccine candidate given alone.

About the PATH Malaria Vaccine Initiative (MVI)
The PATH Malaria Vaccine Initiative (MVI) is a global program established at PATH in 1999 through an initial grant from the Bill & Melinda Gates Foundation. MVI's mission is to accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world. MVI's vision is a world free from malaria. For more information, please visit www.malariavaccine.org.

About PATH
PATH is an international nonprofit organization that creates sustainable, culturally relevant solutions, enabling communities worldwide to break longstanding cycles of poor health. By collaborating with diverse public- and private-sector partners, PATH helps provide appropriate health technologies and vital strategies that change the way people think and act. PATH’s work improves global health and well-being. For more information, please visit www.path.org.

MALARIA: vaccinating the mosquito

William Brieger

O'Neill's approach vaccinates mosquitoes instead of patients. In his lab, under a microscope, workers inject the bacterium Wolbachia pipientis, which is harmless to humans and common among insects, into eggs of Aedes aegypti mosquitoes, a major carrier of the dengue microbe.
O'Neill has found that Wolbachia makes A. aegypti resistant to-and unable to transmit-the disease.
What is more, all progeny inherit immunity.
ScientificAmerican/apr2011/advances
http://www.malariafreefuture.org/blog/

MALARIA: New mosquito type could undermine malaria control

Joanna Carpenter : 4 February 2011

 Bednet use could drive mosquitoes to increasingly bite humans out of doors
Flickr/Georgina Goodwin/Vestergaard Frandsen

Scientists have discovered a new mosquito sub-type that could become a key malaria transmitter out of doors, thus avoiding the mainly indoor control measures, according to a paper published in Science 4th February.
Malaria rates have decreased in many African countries following the widespread use of insecticide-treated bednets and indoor pesticide spraying. But research in Burkina Faso now suggests that up to half of mosquitoes may never enter households and therefore cannot be controlled by nets or sprays.
The finding comes at a time when other researchers are expressing fears that increasing bednet use could drive those mosquitoes that bite indoors into outdoor biting behaviours.
In the Burkina Faso research, scientists took mosquito larvae from ponds near houses and used genetic analysis to identify a recently evolved, sizeable genetic subgroup of Anopheles gambiae s.s. — the most effective transmitter of malaria across Africa. This group has not been detected before, indoors or outdoors.
They found lab-grown adults of this subgroup were highly susceptible to infection by the malaria parasite.
The group does not yet know whether these mosquitoes bite humans: "We're trying to catch them outdoors to see whether we can establish the extent of human feeding," co-author Michelle Riehle, a researcher at the University of Minnesota in the United States, told SciDev.Net.
The research adds to a growing literature that suggests current mosquito control measures may be inadequate. For example, George Christophides, reader in infection and immunity at UK-based Imperial College London, recently co-authored two papers in Science suggesting that the indoor-resting strain of A. gambiae s.s. is diverging into two separate species.
He told SciDev.Net: "Malaria mosquitoes are evolving fast … possibly due to man-made pressures. We know this is happening with insecticides and it may happen with bednets. The more bednets we apply in Africa, the more we may push the mosquitoes to bite outdoors."
Steve Lindsay, professor of public health entomology at the UK's London School of Hygiene and Tropical Medicine, said: "We have very effective controls against A. gambiae s.s., but they're all directed against mosquitoes coming indoors. We're not very good at controlling outdoor biting ... Compliance with repellents is a problem."
Christophides said, "It's very likely we will need a suite of methods depending on what type of mosquitoes we find in each place. Maybe bednets will be functional in one place but not in another."
But transmission-blocking interventions [which interrupt the life cycle of the parasite, which passes from mosquito to human and back again] could be "a universal solution to stop malaria transmission", he said.
Transmission-blocking vaccines or drugs would be given to people to ensure that a mosquito that had bitten a treated person would no longer be able to transmit the disease.
http://www.scidev.net/en/news/new-mosquito-type-could-undermine-malaria-control-1.html

MALARIA: Plasmodium immunomics

01 February 2011 : Denise L. Doolan : International Journal of Parasitology

The Plasmodium parasite, the causative agent of malaria, is an excellent model for immunomic-based approaches to vaccine development. The Plasmodium parasite has a complex life cycle with multiple stages and stage-specific expression of 5300 putative proteins. No malaria vaccine has yet been licensed. Many believe that an effective vaccine will need to target several antigens and multiple stages, and will require the generation of both antibody and cellular immune responses. Vaccine efforts to date have been stage-specific and based on only a very limited number of proteins representing <0.5% of the genome. The recent availability of comprehensive genomic, proteomic and transcriptomic datasets from human and selected non-human primate and rodent malarias provide a foundation to exploit for vaccine development. This information can be mined to identify promising vaccine candidate antigens, by proteome-wide screening of antibody and T cell reactivity using specimens from individuals exposed to malaria and technology platforms such as protein arrays, high throughput protein production and epitope prediction algorithms. Such antigens could be incorporated into a rational vaccine development process that targets specific stages of the Plasmodium parasite life cycle with immune responses implicated in parasite elimination and control. Immunomic approaches which enable the selection of the best possible targets by prioritising antigens according to clinically relevant criteria may overcome the problem of poorly immunogenic, poorly protective vaccines that has plagued malaria vaccine developers for the past 25 years. Herein, current progress and perspectives regarding Plasmodium immunomics are reviewed.

http://www.malarianexus.com/articles/read/123/plasmodium-immunomics/

MALARIA: Plasmodium immunomics

Denise L. Doolan
The Plasmodium parasite, the causative agent of malaria,is an excellent model for immunomic-based approaches to vaccine development. The Plasmodium parasite has a complex life cycle with multiple stages and stage-specific expression of 5300 putative proteins. No malaria vaccine has yet been licensed. Many believe that an effective vaccine will need to target several antigens and multiple stages, and will require the generation of both antibody and cellular immune responses. Vaccine efforts to date have been stage-specific and based on only a very limited number of proteins representing <0.5% of the genome. The recent availability of comprehensive genomic, proteomic and transcriptomic datasets from human and selected non-human primate and rodent malarias provide a foundation to exploit for vaccine development. This information can be mined to identify promising vaccine candidate antigens, by proteome-wide screening of antibody and T cell reactivity using specimens from individuals exposed to malaria and technology platforms such as protein arrays, high throughput protein production and epitope prediction algorithms. Such antigens could be incorporated into a rational vaccine development process that targets specific stages of the Plasmodium parasite life cycle with immune responses implicated in parasite elimination and control. Immunomic approaches which enable the selection of the best possible targets by prioritising antigens according to clinically relevant criteria may overcome the problem of poorly immunogenic, poorly protective vaccines that has plagued malaria vaccine developers for the past 25 years. Herein, current progress and perspectives regarding Plasmodium immunomics are reviewed.
http://www.malarianexus.com/articles/read/123/plasmodium-immunomics/

MALARIA: Malaria vaccine hailed as a succes

Stephen Adams, 14 Jan 2011
A vaccine that almost halves the chance of catching malaria has the potential to save hundreds of thousands of lives a year, say scientists.
Research published online in The Lancet Infectious Diseases indicates that the vaccine reduces the risk of infection by the parasite that causes severe malaria by 46 per cent over 15 months.
Malaria, which is passed to humans via infected mosquitoes, is one of the biggest killers of children in Africa.
Of the 900,000 people killed by the disease across the continent every year, the majority are children under five.
While the vaccine does not give near total protection, as those for other diseases marketed for use in Western countries typically do, it still has the potential to save large numbers of lives.
In the phase II clinical trial, 447 children from Kenya and Tanzania, aged five to 17 months, were given the RTS,S/AS01E vaccine, while the same number were given the rabies vaccine as a 'control' group.
After 15 months, those who had the malaria vaccine were 46 per cent less likely to have been infected with the P Falciparum parasite than the control group. Only 11.4 per cent of those given the vaccine developed clinical malaria, compared to 19.7 per cent of the other group.
Dr Ally Olotu from the Kenya Medical Research Institute-Wellcome Trust Research Programme, who led the study, and fellow authors, concluded that the vaccine provides "sustained efficacy for at least 15 months and shows promise as a potential public health intervention against childhood malaria in malaria endemic countries".
The vaccine works by attacking the parasite when it first enters the bloodstream or liver cells, with the aim of completely preventing infection of red blood cells.
In 2008 results of a small-scale preliminary trial showed that it gave protection to 53 per cent of those vaccinated after eight months. However, the new study is larger, and shows only a small drop in the protection given after a further seven months.
The authors said more work was needed to see how well it worked in HIV-positive and malnourished children.
P falciparum is one of four species of malaria parasite that affect humans. It is found globally but is most common in Africa. It is the only one of the four species that can cause life-threatening malaria, according to the Wellcome Trust.
http://www.telegraph.co.uk/health/healthnews/8257496/Malaria-vaccine-hailed-as-a-success.html

MALARIA: The cost of a malaria-free world

REUTERS : (Additional reporting by Katy Migiro in Kilifi; Editing by Simon Robinson and Sara Ledwith)

Dec. 14, 2010

THE 'E' WORD
It was Gates and his wife Melinda who on Oct. 17, 2007 first dared to revive what in health circles is known as the “e-word” in relation to malaria. Seizing the moment at a meeting of malaria specialists in Seattle, Gates declared: “We will not stop working until malaria is eradicated.” Melinda added that to aspire any lower would be “timid.” The World Health Organization went on to endorse the same ambitious goal.
Talk of eliminating malaria from endemic countries, or eradicating it from the face of the planet, had been considered dangerous and naive ever since a previous project, the Global Malaria Eradication Programme, was abandoned in 1969. That campaign had succeeded in eliminating malaria from Europe, North America, the Caribbean and parts of Asia and South-Central America, but failed to achieve anything like global reach. What was the point of calling for something that was virtually impossible and almost prohibitively expensive?
Richard Feachem, a malaria specialist and director of the Global Health Group at the University of California, San Francisco (UCSF) said the Gates’ speeches were a “shock to the system” for the malaria community. “For a couple of decades before that, the e-words were simply not used in polite company,” he told a recent meeting of malaria specialists in London. “And then suddenly, here were the richest couple in the world with a foundation largely dedicated to global health saying let’s go for eradication.”
Three years on, it’s too early to judge progress — most experts say wiping out malaria could take another 50 years. But scrutinizing the economic realities of eradicating versus controlling malaria has become a pressing question.
One person who has taken a hard look at the costs and benefits of eliminating malaria, versus controlling it at low levels, is the Clinton Health Access Initiative’s Sabot. In a paper published in The Lancet in October, Sabot looked at four malaria-endemic countries — China, Mauritius, Swaziland and Tanzania - to assess the likelihood that, over 50 years, eliminating malaria would save more money than controlling it. He concluded that elimination had a low chance of saving costs in the first three. In Tanzania, he found only a moderate chance that elimination would be cost-saving.
Sabot and others say countries could focus instead on achieving “controlled low-endemic malaria,” where the disease still infects and might still kill, but no longer ranks as a major health concern. “We know that controlling malaria and bringing it from high levels down to negligible levels is a fantastic investment — one of the best buys in global health,” he says.
Several malarial countries — including some in Africa — have already managed to fight the disease down to levels where death rates barely register. South Africa had 37 deaths from malaria in 2007; Swaziland had 14; Botswana only six. In comparison, South Africa had 350,000 AIDS-related deaths in the same year, while Swaziland had around 10,000 and Botswana had around 11,000.
Why pour so much cash into an ideal whose economic benefits can pale against other health problems? That question is especially relevant when you understand it’s the jump from keeping malaria at low levels to eradicating it altogether that makes things really costly. Every single last case has to be tracked down and treated, thousands of blood tests conducted and analyzed for infection; every border crossing and airport monitored to stop new cases coming in.
It is an issue that divides experts. MVI’s Loucq thinks it is a price worth paying and draws a comparison with smallpox. “We know that the first 50% is easy — that’s the low-hanging fruit. The next 25% are very convenient and only a little bit more difficult to get. But the final 1% requires a lot of money and doesn’t look very cost effective,” he says. “For the detection of the last cases, when people were running all over the globe chasing those last few — the costs of that were enormous — but they still did it.”
Sabot says it’s at the point where malaria is barely a problem — even if it remains — that the economic questions get tougher. “How should the global community be spending its limited pot of resources in malaria?” he asks. “It’s a very open question given this uncertainty on cost-benefit, whether those international institutions would want to invest in elimination as opposed to focusing their investments in control, where there is a very well-known and visible high rate of return.”

MALARIA-FREE TOURISM
Of course there are reasons to get rid of malaria — billions of them. In the first part of the 20th century, 178 countries had endemic malaria; now 99 do. Britain and the United States eradicated it in 1952, Australia in 1970. Morocco is the latest place to rid itself of the disease, declaring victory in 2005.
In a recent paper, the UCSF’s Feachem identified 32 countries that have now controlled the disease to a point where they could move towards wiping it out. They are all on the fringes of the malaria map. “More than 2 billion people live in the 32 malaria-eliminating countries,” he said. “The benefit to these individuals, their countries, their neighbouring countries and the world from continuing to shrink the malaria map is clearly large, even if we cannot fully quantify it or express it in terms of U.S. dollars.”
Experts trying to do just that calculate the disease costs African healthcare systems around $12 billion US a year. When you add it all up, malaria lops an estimated 1.3% off annual economic growth in the worst-hit countries, which include the likes of Democratic Republic of Congo and Nigeria. It may not sound much but that’s around half the total rate of growth in gross domestic product that a typical industrialized country might expect outside recession.
Research shows a firm link between reducing the disease and increasing economic output — because workers are healthier and take less time off work. Unsurprisingly, children without malaria do better at school.
Though hard to measure, there are other ways cutting malaria is likely to help. Tourists may be more attracted to parts of Africa that are malaria-free, for instance — a potential boon to places such as Kenya where tourism is one of the main foreign exchange earners. Foreign investors may also be more drawn to countries that have dealt with the problem.

THE SMELL OF WATER
For the people of Kilifi, the debate is little more than a distraction from life’s daily battles. Tourists bathe on the region’s white sand beaches, but most residents struggle to make ends meet by selling charcoal or picking up casual labour.
“Growing up in an average family with many siblings in the house, we knew when the malaria season came and when one of us in the family had a bout of malaria, we knew it was a question of time before it would be the next and the next and the next,” says Roma Chilengi, one of the doctors working on the vaccine trials in the district. “By the time it hits you, you have these terrible fevers, these headaches, and the mere smell of water makes you want to vomit.”
Chilengi is excited about the prospect of the first malaria vaccine, but wary of hoping for too much after years of seeing other measures like mosquito nets, insecticides and anti-malarial drugs fail to end the disease. As for the price, there’s little to dwell on. “All these things cost a lot of money,” he says. “But this money is nothing compared to the burden that malaria hits us with.”
http://chealth.canoe.ca/channel_health_news_details.asp?news_id=31495&rss=67&rid=999999&news_channel_id=1020&channel_id=1020&rot=3

MALARIA: Could malaria vaccine “sit on the shelf”?

13 Dec 2010 : Paul Chinnock
By the year 2015, the first vaccine against malaria could be ready for use on a wide scale. But concerns have been expressed that inadequate planning could prevent it reaching those who are most in need of protection against the disease.
Of several potential malaria vaccines under investigation, the RTS,S vaccine is at the most advanced stage. Its history dates back to research conducted by GlaxoSmithKline and the Walter Reed Army Institute of Research in the mid-1980s. The first human trials began a decade later. A partnership between GSK and the non-profit PATH Malaria Vaccine Initiative (MVI) has made possible its further development.
Phase 3 clinical trials in sub-Saharan Africa began in 2009. Eleven sites in seven countries will enrol a total of 16,000 infants and children. Steps have been taken to expedite the rapid approval of the vaccine by African regulatory authorities, as well as by officials at WHO and the European Medicines Agency, assuming that the trials confirm the effectiveness and safety of RTS,S. It is hoped that this will lead on to the vaccine entering general use as early as 2015.
The level of effectiveness of the vaccine will not be clear until the Phase 3 trials have been completed. It is already apparent that it will not be as effective as vaccines for many other diseases, but a Phase 2 trial in Tanzania [1] found that RTS,S reduced the risk of Plasmodium falciparum infection by 65% and this degree of effectiveness (or even lower) could still save many lives each year. Malaria control programmes would use the vaccine in combination with other tools – residual insecticide spraying of houses, long-acting insecticide-treated bednets, rapid diagnostic tests, and treatment using artemisinin combination therapy.
But the fear of many malaria specialists is that, once the vaccine is ready, health systems in malaria-endemic countries may not be able to bring it into use, because of inadequate preparation. “After decades of research and tens of millions of dollars invested … it would be scandalous if this vaccine just sits on the shelf,” said Yvette Collymore of MVI speaking at a recent conference in Washington DC, USA.
The concern expressed by MVI raises a wider issue. In recent years – with new funding, from sources such as the Gates Foundation and the establishment of a number of public–private product development partnerships – we have seen more R&D efforts targeted on the infectious diseases of poverty. An encouraging number of new tools are now in the development pipeline. But R&D is only the beginning. It will be essential that systems are in place to put the new tools to work and make them available to all those who need them.

Reference
Abdulla S, Oberholzer R, Juma O, Kubhoja S, Machera F et al. (2008). Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. N Engl J Med; 359(24):2533-2544. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19064623

http://www.tropika.net/svc/news/20101213/Chinnock-20101213-News-RTSS

MALARIA: Halting the World's Most Lethal Parasite: Immunizing Mosquitoes and Other "Crazy" Antimalaria Ideas

By Mary Carmichael : November 3, 2010
A new malaria vaccine, a plan to immunize mosquitoes, and other "crazy" ideas have brightened prospects for vanquishing this killer

Vaccines against malaria have encountered repeated failures. New technolo­gical approaches have revived the push for an agent that would provide lifelong immunity.

Late-stage clinical trials will finish this winter on a vaccine that has been under development since the 1980s. It could reduce cases of the most lethal form of malaria by half.
Even as this work moves forward, researchers are proceeding with other strategies for new vaccines, such as a weakened form of the parasite that is cultured in mosquitoes.
Because malaria has been so hard to fight in the past, researchers must moderate outsize expectations to keep hopes from being dashed yet another time if new vaccine candidates fail.
http://www.scientificamerican.com/article.cfm?id=halting-the-worlds-most-lethal-parasite

MALARIA: Trials Advance for a Malaria Vaccine,

Rebecca Voelker
As Trials Advance for a Malaria Vaccine, Policy Makers Urged to Plan for Its Use

As the first promising malaria vaccine makes its way through phase 3 clinical trials in sub-Saharan Africa, stakeholders' greatest fears go beyond the possibility that the vaccine may fail to meet safety and efficacy goals. They worry that even if the vaccine is licensed, inadequate planning for its distribution could leave it to languish in warehouses.
“After decades of research and tens of millions of dollars invested . . . it would be scandalous if this vaccine just sits on the shelf,” said Yvette Collymore, MA, of the nonprofit PATH Malaria Vaccine Initiative (MVI), during a recent Washington, DC, conference.
Clinical trials like this one in Tanzania showed that the RTS,S malaria vaccine has a favorable safety and efficacy profile. The vaccine is now in phase 3 trials.
 (John-Michael Maas/Darby Communications/AP Images)

MVI and the vaccine's creator, GlaxoSmithKline (GSK) Biologicals, partnered in 2001 to develop the vaccine for infants and young children in sub-Saharan Africa.
http://jama.ama-assn.org/content/304/21/2348.extract

MALARIA: Malaria in the Military

 Bill Brieger

11 Nov 2010



November 11th is Veteran’s Day in the United States. Over the years soldiers have been vulnerable to malaria. During the U.S. Civil War 150 years ago over 14,000 Union troops are estimated to have died from malaria. While death estimates were not available for the Confederates, it was thought that over 40,000 malaria cases occurred in an 18-month period in the middle of the war.

Today places like Afghanistan and the Horn of Africa pose a malaria threat to troops, so there is malaria prophylaxis for soldiers. Sometimes the prevention itself poses problems. “The Army has dropped Lariam — the drug linked to side effects including suicidal tendencies, anxiety, aggression and paranoia,” and now prefers doxycycline for people who may react to mefloquine.
The military takes malaria seriously now. The Walter Reed Army Institute of Research (WRAIR) puts a priority on malaria research since, “Malaria remains highly relevant to the military because of its prevalence, variety (there are four species that infect humans), debilitating nature, potential lethality, and tendency to become resistant to drugs. No organization in the world has WRAIR’s experience in the complete spectrum of malaria research.”
WRAIR’s “Work on a vaccine is also progressing. Advanced molecular, genetic, and biomedical technologies are now being employed to produce candidate malaria vaccines. Field trials of these candidate pharmaceuticals are an essential part of the program and are underway in Thailand and Kenya.”
The military of all nations are at risk when they serve in malaria endemic areas. For example, a Philippine soldier “succumbed to malaria on 23 October 2008 while serving as a military observer with the U.N. Mission in Sudan.”
Another concern of malaria in the military is the potential for soldiers who contract malaria for spreading it to other countries or bringing it home. It was reported that Soviet soldiers serving in Afghanistan some years ago brought the disease back to republics in the Caucasus and Central Asia. Though this particular spread could be controlled, not all situations may be so fortunate.
Today a variety of injury and mental health problems may overwhelm the effects of malaria on soldiers. Still, soldiers are at risk. For example in 2002, “38 cases of malaria were identifiedin a 725-man Ranger Task Force that deployed to eastern Afghanistan.” Also over a 6-year span the Defense Medical Surveillance System reported 423 cases of malaria including Plasmodium vivax, P. falciparum, P. ovale, and P. malaria. A big challenge is the inability of health systems in non-endemic countries to treat and save lives of soldiers who return home with the disease.
There are basically two lessons from this issue. First malaria control must recognize that soldiers who may not be immune when they enter a malaria endemic war zone are at risk of malaria death. Secondly, as a mobile population soldiers have the potential for reintroducing malaria to areas where it may have been eliminated. War kills people; malaria kills people - when soldiers are infected a double dose of death potentially occurs
http://www.malariafreefuture.org/blog/?p=1080

MALARIA: Malaria vaccine trial disappoints

Maggie Fox
29 Sep 2010
The numbers were so bad that Dr. Stephen Hoffman did not even want to say them out loud.
"It was a low number," he said. Pressed, he added, "Only a handful." Finally he squeezed the numbers out. "We had five."
Out of 80 volunteers vaccinated with Sanaria's experimental malaria vaccine, only five were protected from infection in the company's first clinical trial.
The Maryland-based company, which opened its doors in 2007, has not given up. But its disappointing results illustrate the uphill battle to develop a vaccine against an infection that kills 800,000 people a year, most of them young African children.
Hoffman gave details about what his team of scientists learned from the trial at a conference of malaria vaccine makers and their backers being held in Washington this week.
Tests in animals suggest that perhaps giving the vaccine intravenously might provide better protection, and Hoffman, founder and chief executive of the small, privately held company, is planning ways to test the idea in people.
"The vaccine was used to immunize 80 volunteers and it was safe and well tolerated," he said in an interview. It did, as expected, stimulate an immune response against the malaria parasite - just not nearly as much as Hoffman had hoped.
Now Sanaria has run out of money from the non-profit PATH Malaria Vaccine Initiative. But Hoffman plans to continue with cash from the U.S. National Institutes of Health and perhaps other government agencies.
"Right now I do need to get a lot more funds," he said.
A malaria vaccine has been the dream of hundreds of experts but has been maddeningly hard to actually develop.
Malaria is caused by a parasite, and making a vaccine against parasites is much harder to do than vaccinating against one-celled organisms like bacteria, or the even simpler viruses.
Plus malaria, which is spread by mosquitoes, has a complicated life cycle, passing from the blood to the liver to other organs.
GETTING CLOSE
GlaxoSmithKline is testing what most experts consider the most promising malaria vaccine, one called RTS,S or Mosquirix.
"We're getting close - we are getting very close," Glaxo's Dr. Joe Cohen said in an interview.
Investigators in seven African countries have enrolled 12,000 children and need just 4,000 more. The first data on safety and efficacy are expected by the end of next year.
In earlier trials, the vaccine appeared to produce a good immune response in African children.
But the goal is set very low - the Malaria Vaccine Initiative is asking only for it to protect 50 percent of the children against severe disease for a year.
"We are looking into the possibility of a next-generation," vaccine," said Cohen. Glaxo has spent about $300 million on Mosquirix, plans to spend about another $100 million and will receive an additional $100 million or so from the non-profit Bill & Melinda Gates Foundation, for a total of $500 million.
Investigators at the conference swapped notes on Tuesday and Wednesday about what the trials have told them so far about trying to vaccinate against the Plasmodium falciparum parasite, which causes most cases of malaria.
And groups presented ideas for new ways to deliver vaccines - such as Pennsylvania-based Inovio Biomedical Corp, which is using its so-called electroporation delivery-DNA vaccine approach to try to make a vaccine against malaria, as well as flu and AIDS vaccines.
Electroporation involves making tiny holes in the skin instead of using a needle to deliver a vaccine.
Dutch biotechnology company Crucell has technology that uses a common cold virus called an adenovirus that can "prime" the immune system and may help get a better response to Glaxo's Mosquirix. Crucell has teamed up with Glaxo to test the two together.
Johnson & Johnson, which already owns nearly 18 percent of Crucell, said this month it planned to buy the Dutch vaccine maker for $2.3 billion.
Then there is the next goal, said Cohen - a vaccine against Plasmodium vivax, the parasite that causes most cases of malaria in Asia.
http://www.fightingmalaria.org/news.aspx?id=1516

MALARIA: Malaria vaccine closer than ever, scientists say

Karin Zeitvogel (AFP)


WASHINGTON — Scientists are closer than ever to rolling out the first malaria vaccine, which could be available in Africa by 2015, a co-inventor of the shot against the killer disease said Tuesday.

Advanced trials of the RTS,S vaccine against falciparum malaria, the deadliest strain of the disease, are under way in seven African countries and going "very well," said GlaxoSmithKline researcher Joe Cohen, who has been working on developing the vaccine for over 20 years.

"We believe we'll have the first data coming out of the trials in 2012, and, to make a long story short, we could have the first implementation in Africa between 2015 and 2016," he told AFP.

Cohen was speaking at a conference in Washington examining ways to beat malaria.

Some 12,000 children have already been enrolled in the Phase III trials in Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique and Tanzania, which have an enrollment target of 16,000 children.

The trial protocol varies from country to country -- even from village to village -- to take into account cultural sensitivities, but the basics are the same, said Ghana clinical epidemiologist Kwaku Poku Asante and Ally Olutu, a clinician from Kenya. The pair are working on the vaccine trials.
Children have to be in good health to join the trial, and will be followed up for 32 months, Asante said.
The results of smaller-scale phase II trials, which were announced in 2008, showed RTS,S was 53 percent effective against clinical falciparum malaria in young children and up to 65 percent effective in infants, the two groups most at-risk from the parasitic disease.

If RTS,S passes muster in the phase III trials and is licensed, it "will save many, many hundreds of thousands of lives in Africa," even if it is only partially effective against malaria, said Cohen.

But completing the vast trial in Africa and rolling out the vaccine will not signal an end to the process to develop malaria vaccines, he and other researchers warned.

RTS,S is only a stepping stone to wiping out the disease that threatens more than a third of the world's population and kills some 900,000 people a year, most of them in Africa.
According to organizers of the Washington conference, some 200 people die of malaria every hour of every day every year, most of them children in Africa.
Malaria is one of the main obstacles to socio-economic development in Africa, and developing effective vaccines against the disease would have an enormous effect on reducing its negative impact, they said.

"We must look ahead to an even better second generation vaccine, one that is maybe 80 percent effective," said Cohen.

"That vaccine could address the malaria parasites that are prevalent elsewhere in the world, such as Asia and Latin America, where the plasmodium vivax parasite predominates."

But he worried the global economic slump could put the brakes on malaria vaccine research.

"The financial crisis has had a big impact on the package of money that's available," said Cohen.
"Vaccines against other diseases that are ready to be implemented in Africa are being delayed because financing is not available," he added, warning the same could happen to RTS,S if there is no money available for a wide-scale roll-out after it is approved.
PATH Malaria Vaccine Initiative (MVI) director Christian Loucq urged investors from the public and private sectors who teamed up to help make the RTS,S more than just a glint in Cohen's eye to keep investing in malaria research even after the first vaccine becomes reality.

Funding is needed, for instance, to develop a way to "protect the mosquito," said Loucq.

Mosquitoes get the malaria parasite when they bite an infected person, and then pass it back into the human chain when they bite someone else, Loucq explained.

"If you can effectively and widely prevent transmission from human to mosquitoes, you will prevent transmission of the disease. We believe that is our biggest hope for achieving our ultimate goal -- eliminating malaria -- but that's not going to happen before 2025," he said.

"In the meantime, if we forget to keep investing in research we might, like we did in the '60s, once again lose the battle against malaria."
http://www.google.com/hostednews/afp/article/ALeqM5hDd-wIF22ngXvkXIF1bUXxXiEXmQ?docId=CNG.6d8134b4ddb27ece50584ad27507f332.b61

MALARIA: Can Malaria Be Beaten?

Jeremy Laurance 05 Aug 2010 The Independent
When I see a packet of malaria pills I think of that famous Clint Eastwood line from Dirty Harry, delivered as he pointed his .44 magnum at a bank robber and neither of them could remember how many shots he had fired, or whether there was still one left in the chamber. "The question you have got to ask yourself is: do I feel lucky? Well, do ya, punk?"Actually, I do. Lucky enough not to have to take the nasty, expensive little things on my periodic visits to Africa and other malarial parts of the world. Now I find myself being asked to reconsider after X Factor star Cheryl Cole's unpleasant encounter with a mosquito in Tanzania. Such is the power of celebrity.I based my view on a Lancet paper published in the 1990s by London's Hospital for Tropical Diseases which assessed the chances of contracting malaria, for those not taking prophylactic drugs, at 0.6 per cent for an average two-week holiday in East Africa. The authors described this as "high" and in public health terms I suppose it is - the Health Protection Agency points out that more than 1,500 people are diagnosed with malaria in the UK each year having acquired it abroad.But it didn't seem high to me - and I disliked the way commercial travel clinics pushed expensive injections and other protective measures at frightened travellers without quantifying the risks. So for the last 15 years I have followed a rough rule of thumb: if I am slumming it or travelling into the bush, I take the pills; if I am staying in four-star hotels in town, I don't bother. My impression is that many regular visitors to Africa do the same. Public health doctors may demur - and Ms Cole's story undoubtedly strengthens their case. She had spent only six days in Tanzania and had, reportedly, taken anti-malarial drugs that provide 90 per cent protection. How unlucky is that?Doubly unlucky because - and this is the real story about malaria - in many parts of the world it is declining, rapidly. About 2.5 billion people live in malarial areas around the globe, and the disease kills almost a million of them every year, mostly children. Changes in the incidence of the disease may go unnoticed by tourists but have huge significance for the local population. Now Cheryl Cole, who first visited Tanzania last year on a charity expedition to Mount Kilimanjaro, has helped focus attention on their plight in a way she could hardly have anticipated.In coastal Kenya, not far from where she was holidaying, cases of severe malaria in children have fallen 90 per cent in the last five years. Similar falls have been reported from other locations across Africa and the world.In certain islands in the Philippines malaria has been eliminated. Mexico is said to be close to eradication, and some countries in Central and South America are moving in the same direction. Morocco was recently declared malaria-free by the World Health Organisation, helping boost the tourist trade there.Sub-Saharan Africa, which bears 70 per cent of the disease burden, presents a much tougher challenge. Yet even here there have been spectacular advances, as in coastal Kenya. Last week, the African Leaders Malaria Alliance announced that malaria cases and deaths had been cut by up to 80 per cent in 10 African countries since 2000, including Ethiopia, Ghana, Rwanda, Zambia and Zanzibar.Among malaria specialists, where gloom prevailed a decade ago, the buzzword now is "elimination": no more malaria deaths by 2015 and no more malaria a decade or two after that. As the Lancet noted last month, "previously cautious malariologists, released from a 40-year collective depression... have been invigorated."How has this change of heart come about? Some call it the Bill Gates effect. Almost three years ago, the world's biggest philanthropist threw down a challenge to the global health community to eliminate malaria in his lifetime. Sceptics responded that his dream would only be realised if he were cryo-preserved. Yet his call had a galvanising effect.The Foundation that he leads with his wife, Melinda, has not only given grants of dizzying size to the search for a malaria vaccine, the distribution of bed nets and other measures, it has also brought a new vigour to the entire aid industry. Its speed and flexibility leaves larger bureaucracies like the UN standing, and where it goes others follow. It has been described as a new type of multilateral organisation, introducing entrepreneurial flair to a sector submerged in red tape.Some complain that Gates is seeking to replicate the world domination he achieved with Microsoft in another, albeit altruistic, sphere. These critics say the new entrepreneurial aid business he has spawned is undemocratic, overly powerful, and is leading to empire- building, wasteful competition, fragmentation and duplication. Why should Bill Gates decide which sorts of vaccines get developed? they ask.There is no denying, however, the impact of Gates's interest on the bottom line. Today's funding for malaria, from all sources, exceeds $10bn (£6.3bn) - a hundredfold increase in little more than a decade. Celebrities from Senegalese musician Youssou N'Dour to David Beckham have joined the cause. Politicians Bill Clinton and Tony Blair have become involved through their respective aid foundations, followed by a growing queue of corporate donors and public figures who bring clout, profile and funding. This week, Andrew Mitchell, the International Development Secretary, published the UK's business plan for malaria, opening a consultation on the best ways of supporting the fight against the disease.Malaria - for so long the poor relation to Aids in terms of global attention, despite claiming more lives in many countries - is suddenly glamorous.The tools for elimination are to hand. More than 200m insecticide-treated bed nets have been distributed since 2000, and are estimated to have saved 1m lives, according to the Roll Back Malaria Partnership. Ban ki-Moon, the UN Secretary General, said that with the delivery of a further 150m bed nets by the end of this year "universal coverage of malaria prevention can be achieved". Vast funds have been invested in indoor spraying against mosquitoes, in distributing more effective artemesinin-based drugs against the disease, and in developing a vaccine, with one candidate, made by the UK-based pharmaceutical manufacturer GlaxoSmithKline, in final (phase III) human trials.But meeting Gates's challenge will be a tough task. Optimists, such as Sir Richard Feachem of the Malaria Elimination Group, point to the "shrinking map" of malaria, which included the US and the UK in 1900 (when malaria was endemic in the Kent marshes). Today, 108 countries in the world are malaria-free. One hundred countries have continuing malaria transmission, and of these, 39 are embarked upon malaria elimination. The remaining 61 are striving to control malaria, but it is Feachem's hope that they too can be persuaded to switch to a policy of elimination.The task is immense. In 2008, malaria killed 863,000 people. Almost 90 per cent of those who died were in Africa, and of those, almost 90 per cent were children under five, according to the WHO. Children are especially vulnerable because they have undeveloped immune systems; the WHO estimates the disease kills 3,000 children a day.The world has been striving to eliminate malaria for more than half a century - with faint success. The Global Malaria Eradication Programme was launched in 1955 but it quickly became apparent that its ambition was not achievable in sub-Saharan Africa. In the late Sixties the strategy switched from eradication to long-term control; people with fever caused by the disease were treated with the then standard drug, chloroquine. But as resistance to the drug grew, malaria deaths rose through the 1970s and 1980s. By the early 1990s the strategy was recognised as a disaster.Throughout the 1990s, as nations wrung their hands over Aids, efforts were made to refocus attention on malaria. The world's health ministers launched a global declaration in Amsterdam in 1992 to control the disease, with a focus on Africa. The latest drive against the disease began 10 years ago, when leaders of countries across Africa signed a declaration in Abuja, Nigeria to "halve the malaria mortality for Africa's people by 2010". Initially progress was slow; there were reports that instead of declining, malaria was rising, by up to half in some areas. Accurate figures were hard to come by, and estimates were distrusted. What is not in dispute, however, is that over the last three years things have moved much more quickly, and more consistently in the right direction. The huge rise in the importation of bed nets and artemesinin drugs has saved millions of lives.Controlling malaria has come to be seen as good business, not just good charity. The disease is estimated to cost Africa $12bn a year - 1.3 per cent of its economic growth. If that sum could be saved, it would constitute the biggest boost to health and development in the continent's history. Eradicating disease boosts productivity, creates markets and stabilises governments.The future, however, is anything but certain. Though the 90 per cent fall in children with severe malaria on the Kenyan coast is impressive, the reasons are not obvious. Malaria has been in decline in this area for at least 15 years and some have suggested climate change is a factor. Meanwhile it is rising in upland areas around Mount Kenya, where incidence was previously low. Professor Robert Snow, who reported the Kenyan figures in The Lancet, said malaria had changed "from a major cause of childhood illness and death to a relatively minor problem" on Kenya's coast. But it was simplistic to attribute it to more bed nets and better drugs. "The truth is probably much more complex," he wrote.Critics also question the notion of "universal coverage" with bed nets - expected in Ethiopia and southern Sudan this year and everywhere in early 2011. How many nets can you hang in a small hut occupied by a large family? Some older children are always likely to go without. There have been distribution problems too: the rush to freight in bed nets has left thousands of them sitting in warehouses because there was no means of transporting them over the final miles.Malaria is concentrated around the equator, the "middle, wet bit" of Africa, with just seven countries accounting for two thirds of all cases: the Democratic Republic of Congo, Ethiopia, Kenya, Nigeria, southern Sudan, Tanzania and Uganda. While there have been gains in some, others such as Nigeria have done less well. With a population of 120 million, Nigeria contributes heavily to the global malaria burden.Even where success has been achieved, there is no guarantee it will be permanent. Zanzibar, the island off Tanzania that has become a luxury tourist destination, has eliminated malaria twice before but each time it has been re-imported from the mainland. Kenya has also slipped back, and in Congo the uncertainties multiply.Constant vigilance is essential. That requires stable, committed government. It is not always available. In Uganda, grants worth over $350m were suspended by the Global Fund over allegations of corruption (which are currently before the courts). In Tanzania a grant worth over $100m from the Global Fund was discovered unclaimed last year because it lacked a single signature.Countries worst affected by the disease have been reluctant to buy the new artemesinin-based drugs because of their cost. At $1 to $2 a dose, they are 10 times more expensive than chloroquine. Though funded by aid programmes today, governments wonder for how long that funding will last. There are fears about resistance too, signs of which have emerged on the Thai-Cambodian border. If the artemesinin drugs lose their potency, there is nothing else immediately in the pharmaceutical locker.Eradication may be the only way to combat resistance. The most taxing question, however, and one which divides the malaria community, is what penalties may follow success? Chris Drakeley, director of the Malaria Centre at the London School of Hygiene and Tropical Medicine, points out that enormous funds are required to eliminate the last few cases of a disease - witness polio, still defying efforts to wipe it from the planet."If malaria drops down the Top 10 list of worst diseases, what justification is there for putting in vast resources to eliminate it? In a situation where malaria had been controlled to a low level for a decade, you would have a large group of children with no immunity to the disease. The impact of an outbreak could then be devastating. There is an argument that some level of malaria is quite good - it maintains a level of immunity in the population."The best hope for the future is a vaccine. No disease has ever been eliminated without a vaccine. But malaria is not caused by a simple virus - it is an organism (a parasite) with a nucleus that is more complex than a virus.The front runner is GlaxoSmithKline's RTSS vaccine, currently being tested in 14,000 children in 11 African countries, with results due in 2012. Early trials suggested that it provided 30-50 per cent protection - far from perfect, but a lot better than nothing.Scientists are optimistic that it will provide a useful further weapon against malaria. But there will be many years yet of fighting before the war can be declared won.
http://www.independent.co.uk/life-style/health-and-families/features/can-malaria-be-beaten-2043383.html